Species sensitivity distributions for two widely used anti-sea lice chemotherapeutants in the salmon aquaculture industry.

The main objective of the present study is to construct acute aquatic species sensitivity distributions (SSD) and generate proposed HC5 values (i.e. the hazardous concentration for which 5 % of species are affected or potentially affected) for two aquaculture anti-sea lice bath pesticides, azamethiphos, and hydrogen peroxide. These values could be used as the basis for the establishment of environmental quality standards (EQS). We have generated SSDs and inferred HC5 values for mortality and sublethal endpoints using LC50, EC50, and NOEC/LOEC data points separately and for each bath pesticide. Through the examination of literature data on the toxicity of both compounds, we opted to use tests with limited exposure times to ensure environmental relevance for bath pesticides. We also separated life stages for some of the sensitive taxa to account for differences in sensitivities and risk of exposure. The resulting threshold concentrations in environmental seawater are 0.10 µg/L for azamethiphos and 0.15 mg/L for hydrogen peroxide. These suggested azamethiphos and hydrogen peroxide thresholds are comparable to some previously reported EQS values. Further considerations need to be included in how to better use these thresholds in a regulatory context in relation to dispersion patterns. It is also clear that delayed mortality and sublethal effects documented in the literature require further study to fully anticipate the environmental risks of using these two bath pesticides.

Recent Developments in Species Sensitivity Distribution Modeling.

The species sensitivity distribution (SSD) is a statistical approach that is used to estimate either the concentration of a chemical that is hazardous to no more than x% of all species (the HCx) or the proportion of species potentially affected by a given concentration of a chemical. Despite a significant body of published research and critical reviews over the past 20 yr aimed at improving the methodology, the fundamentals remain unchanged. Although there have been some recent suggestions for improvements to SSD methods in the literature, in general, few of these suggestions have been formally adopted. Furthermore, critics of the approach can rightly point to the fact that differences in technical implementation can lead to marked differences in results, thereby undermining confidence in SSD approaches. Despite the limitations, SSDs remain a practical tool and, until a demonstrably better inferential framework is available, developments and enhancements to conventional SSD practice will and should continue. We therefore believe the time has come for the scientific community to decide how it wants SSD methods to evolve. The present study summarizes the current status of, and elaborates on several recent developments for, SSD methods, specifically, model averaging, multimodality, and software development. We also consider future directions with respect to the use of SSDs, with the ultimate aim of helping to facilitate greater international collaboration and, potentially, greater harmonization of SSD methods. Environ Toxicol Chem 2021;40:293-308. © 2020 SETAC.

Subfertile female androgen receptor knockout mice exhibit defects in neuroendocrine signaling, intraovarian function, and uterine development but not uterine function.

Female androgen receptor (AR) knockout mice (AR(-/-)) generated by an in-frame Ar exon 3 deletion are subfertile, but the mechanism is not clearly defined. To distinguish between extra- and intraovarian defects, reciprocal ovarian transplants were undertaken. Ovariectomized AR(-/-) hosts with wild-type (AR(+/+)) ovary transplants displayed abnormal estrus cycles, with longer cycles (50%, P < 0.05), and 66% were infertile (P < 0.05), whereas AR(+/+) hosts with either AR(-/-) or surgical control AR(+/+) ovary transplants displayed normal estrus cycles and fertility. These data imply a neuroendocrine defect, which is further supported by increased FSH (P <0.05) and estradiol (P <0.05), and greater LH suppressibility by estradiol in AR(-/-) females at estrus (P <0.05). Additional intraovarian defects were observed by the finding that both experimental transplant groups exhibited significantly reduced pups per litter (P < 0.05) and corpora lutea numbers (P < 0.05) compared with surgical controls. All groups exhibited normal uterine and lactation functions. AR(-/-) uteri were morphologically different from AR(+/+) with an increase in horn length (P < 0.01) but a reduction in uterine diameter (P < 0.05), total uterine area (P < 0.05), endometrial area (P < 0.05), and myometrial area (P < 0.01) at diestrus, indicating a role for AR in uterine growth and development. Both experimental transplant groups displayed a significant reduction in uterine diameter (P < 0.01) compared with transplanted wild-type controls, indicating a role for both AR-mediated intraovarian and intrauterine influences on uterine physiology. In conclusion, these data provide direct evidence that extraovarian neuroendocrine, but not uterine effects, as well as local intraovarian AR-mediated actions are important in maintaining female fertility, and a disruption of AR signaling leads to altered uterine development.